CN111788188A

CN111788188A - Method for producing a fuel additive

Info

Publication number: CN111788188A
Application number: CN201880090136.2A
Authority: CN
Inventors: S·V·菲利普
Original assignee: BP Oil International Ltd
Current assignee: BP Oil International Ltd
Priority date: 2017-12-27
Filing date: 2018-12-19
Publication date: 2020-10-16
Also published as: GB201721964D0; RU2020124086A; US11384057B2; US20200331869A1; EP3732172A1; WO2019129591A1; JP2021507930A

Abstract

A process for preparing a fuel additive having formula (1) is provided. The method comprises effecting the following reaction: (i) adding an alkylating agent b to the starting materiala: (a) to form an intermediatec(ii) a And (ii) reacting the intermediatecClosed-loop to form fuel additivese。

Description

Method for producing a fuel additive

Technical Field

The present invention relates to a method for preparing an octane boosting additive for use in a fuel for a spark-ignition internal combustion engine. In particular, the present invention relates to a process for the preparation of octane boosting additives which are derivatives of benzo [1,4] oxazines and 1, 5-benzoxazepinones. The invention also relates to a method for preparing a fuel for a spark-ignition internal combustion engine comprising said octane boosting additive.

Background

Spark ignition internal combustion engines are widely used for domestic and industrial power. For example, spark ignition internal combustion engines are commonly used in the automotive industry for powering vehicles such as passenger cars.

Fuels for spark-ignition internal combustion engines, typically gasoline fuels, typically contain a number of additives to improve fuel properties.

One class of fuel additives is octane improving additives. These additives increase octane number for the fuel, which is desirable to combat problems associated with pre-ignition, such as knock. When the base fuel octane is too low, the addition of an octane improver to the fuel can be performed by a refinery or other supply (suppier), such as a fuel terminal or a bulk fuel mixer, so that the fuel meets the appropriate fuel specifications.

Organometallic compounds containing, for example, iron, lead or manganese are well known octane improvers, of which Tetraethyllead (TEL) has been widely used as a high-efficiency octane improver. However, TEL and other organometallic compounds (if present) are currently commonly used in fuels only in small amounts because they can be toxic, damaging to the engine and damaging to the environment.

Octane improvers that are not metal-based include oxygenates (e.g., ethers and alcohols) and aromatic amines. However, these additives also have various disadvantages. For example, N-methylaniline (NMA) (aromatic amine) must be used at relatively high treat rates (1.5 to 2% additive weight/base fuel weight) to have a significant effect on the octane number of the fuel. NMA may also be toxic. Oxygenates reduce the energy density in the fuel and can cause compatibility problems in fuel storage, fuel lines, seals and other engine components when it comes with NMA that must be added at high processing rates.

Recently, a new class of octane boosting additives has been discovered. These octane boosting additives are derivatives of benzo [1,4] oxazines and 1, 5-benzoxazepines and show great promise due to their non-metallic nature, their low oxygenate content and their efficacy at low treat rates (see WO 2017/137518).

The synthetic routes currently reported in the literature provide various descriptions of how benzoxazines can be prepared on a relatively small scale (from a few hundred mg to a scale of up to 100 kg). For example, US 2008/064871, which relates to compounds for the treatment or prevention of uric acid related diseases such as gout, discloses the preparation of benzoxazine-derived compounds.

However, due to the high cost of specialized raw materials (e.g. methylaminophenols) and reagents (e.g. lithium aluminium hydride and dibromoethane), which are required in stoichiometric amounts, such synthetic methods are not useful for preparing new types of octane boosting additives on an industrial scale (e.g. from 50 up to 20,000 metric tons/year).

Thus, there is a need for a process for the synthesis of a new class of octane boosting additives that can be implemented on a large scale and that alleviates at least some of the problems highlighted above (e.g., by avoiding the use of expensive aminophenol starting materials).

Summary of The Invention

It has now been found that a new class of octane boosting additives can be prepared from starting materials derived from nitrophenols and nitroanilines. Accordingly, the present invention provides a process for preparing a fuel additive having the formulaeThe method of (1):

wherein: r₁Is hydrogen;

R₂、R₃、R₄、R₅、R₁₁and R₁₂Each independently selected from hydrogen, alkyl, alkoxy-alkyl, secondary amine, and tertiary amine groups;

R₆、R₇、R₈and R₉Each independently selected from hydrogen, alkyl, alkoxy-alkyl, secondary amine, and tertiary amine groups;

x is selected from-O-or-NR₁₀-, wherein R₁₀Selected from hydrogen and alkyl; and

n is 0 or 1.

The method comprises effecting the following reaction:

(i) adding an alkylating agent b to the starting materiala：

To form an intermediatec(ii) a And

(ii) making the intermediatecClosed-loop to form fuel additivese，

Wherein alkylating agent b and intermediate c are selected from:

wherein: each L in alkylating agent b is independently selected from a leaving group or two L groups together form a group-O-c (O) -O-;

each R₁₃Independently selected from hydrogen and alkyl, or two R₁₃The groups together with the-O-C-O-group to which they are attached form a 1, 3-dioxolane or 1, 3-dioxane group; and

R₁₄selected from hydrogen and alkyl.

Also provided is a fuel additive obtainable by the process of the inventione。

The invention also provides a method for preparing a fuel for a spark-ignition internal combustion engine. The method comprises the following steps:

preparing a fuel additive using the method of the invention; and

blending the fuel additive with a base fuel.

Fuel for a spark-ignited internal combustion engine is also provided. The fuel comprises the fuel additive of the inventioneAnd a base fuel.

Detailed description of the invention

The present invention provides a method for preparing a fuel additive.

In step (i) of the process, an alkylating agent is addedbAdding the starting materialsaTo form an intermediatec:

。

In embodiment (1), the alkylating agent b is:

and intermediate c is:

. This embodiment is particularly preferred.

In embodiment (2), the alkylating agent b is:

and intermediate c is:

。

in embodiment (3), the alkylating agent b is:

and intermediate c is:

。

each R₁₃Independently selected from hydrogen and alkyl, or two R₁₃Radicals with-O-C to which they are attachedthe-O-groups together form a 1, 3-dioxolane or 1, 3-dioxane group. Each R₁₃Preferably selected from hydrogen, methyl, ethyl, propyl and butyl, and more preferably methyl and ethyl. In a preferred embodiment, said R is₁₃The groups are the same.

In embodiment (4), the alkylating agent b is:

and intermediate c is:

. Preferably, the alkylating agent b is an epoxide reagent, i.e. n = 0, since epoxides readily react with the starting material a to form intermediatesc。

In embodiment (5), the alkylating agent b is:

and intermediate c is:

。

R₁₄selected from hydrogen and alkyl groups, and preferably hydrogen, methyl, ethyl, propyl and butyl, and more preferably hydrogen, methyl and ethyl.

In embodiment (6), the alkylating agent b is:

and intermediate c is:

。

in step (i), the leaving group L is lost from the alkylating agent b. Each L in alkylating agent b is independently selected from a leaving group or two L groups together form a group-O-c (O) -O-, i.e., a group effective to provide 2 leaving groups. It is to be understood that only two L groups are present in embodiment (2) and thus together may form the group-O-C (O) -O-.

Preferably, each L is independently selected from the group consisting of halides (e.g., Cl, Br, I), sulfonates (e.g.-OSO₂A, wherein A is selected from tolyl, methyl, -CF₃、-CH₂Cl, phenyl and p-nitrophenyl), substituted aryloxy (e.g. phenyl-O-Ar, wherein Ar is selected from nitro substituted aryl such as p-nitrophenyl) and hydroxyl, more preferably from halides and sulfonates, and most preferably from Cl and Br. The hydroxyl group is generally used only as a possible leaving group L in embodiment (2).

Generally, relative to the starting materialsaThe alkylating agent may be used in an amount of 0.5 to 8 molar equivalents, preferably 0.75 to 6 molar equivalents and more preferably 0.85 to 5 molar equivalentsb. It is understood that the starting materialsaAnd an alkylating agentbThe preferred ratio of (b) may vary between different embodiments. For example, for embodiment (1), the alkylating agent may preferably be used in an amount of 0.85 to 0.95 molar equivalentsb. For embodiment (2), the alkylating agent may preferably be used in an amount of 2 to 5 molar equivalentsb。

Step (i) of the present invention is preferably carried out in the presence of a base. This applies in particular to embodiments (1), (2) (in particular in the case other than where two L groups together form the group-O-C (O) -O-or where two L groups are selected from-OH), (3), (5) and (6). Suitable bases may be selected from:

inorganic bases, for example alkali metal hydroxides such as sodium hydroxide and potassium hydroxide and carbonates such as sodium bicarbonate, sodium carbonate, potassium bicarbonate and potassium carbonate,

-ammonia, and

organic bases, for example nitrogen-containing organic bases, such as from trimethylamine, diisopropylethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, pyridine and 4-dimethylaminopyridine.

The base is preferably an inorganic base and more preferably selected from carbonates.

Relative to the starting materialsaPreferably in an amount of 0.8 to 5 molar equivalents, preferably 1 to 3 molar equivalents and more preferably 1.05 to 2.5 molar equivalentsThe base is described.

In some embodiments, step (i) may be effected in the presence of a catalyst, for example a catalyst selected from the group consisting of acids (e.g. p-toluenesulfonic acid or sodium bisulfite), zeolites (e.g. zeolite Y, sodium (faujasite)), metal catalysts (e.g. palladium catalysts, preferably used with a zinc oxide support), halogen exchange catalysts (e.g. alkali metal halides such as KBr, NaBr, KI and NaI), and phase transfer catalysts (e.g. quaternary ammonium salts such as tetraalkylammonium halides, preferably butyltriethylammonium chloride or methyltributylammonium chloride).

For example, in embodiment (2) wherein two L groups together form the group-O-c (O) -O-, or wherein at least one L group is selected from-OH, then a catalyst is preferably used and preferably selected from an acid (e.g. p-toluenesulfonic acid or sodium bisulfite), a zeolite (e.g. zeolite Y, sodium (faujasite)) or a metal catalyst (e.g. a palladium catalyst, preferably used with a zinc oxide support).

In embodiments wherein L is halogen, particularly where L is Cl, step (i) may also be effected in the presence of a catalyst, for example in the presence of at least one and preferably both of a halogen exchange catalyst (e.g., an alkali metal halide such as KBr, NaBr, KI and NaI) and a phase transfer catalyst (e.g., a quaternary ammonium salt such as a tetraalkylammonium halide, preferably butyltriethylammonium chloride or methyltributylammonium chloride).

Relative to the starting materialsaThe catalyst may be used in an amount of less than 1 molar equivalent, preferably less than 0.5 molar equivalent and more preferably less than 0.1 molar equivalent.

It is understood that a base and a catalyst may be used. An example of such a combination is an inorganic base (e.g., an alkali metal carbonate) and a halogen exchange catalyst (e.g., an alkali metal iodide).

Step (i) may be carried out in the presence of a solvent selected from aprotic solvents (e.g., tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, ethylene carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran (oxolane) and propionitrile), chlorinated solvents (e.g., dichloromethane, dichloroethane, chloroform) and water. Aprotic solvents are well known in the art as solvents that cannot donate protons. Aprotic solvents do not contain hydrogen atoms bound to nitrogen or oxygen.

Preferably, step (i) is effected in the presence of an aprotic solvent.

Preferably, the solvent of each of embodiments (1) to (6) is selected from:

for embodiment (1) aprotic solvents (e.g., from acetonitrile, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, and acetone);

for embodiment (2), except where two L groups together form the group-O-c (O) -O-or at least one L group is selected from-OH, and embodiments (3) and (6) aprotic solvents (e.g., from tetrahydrofuran, acetonitrile, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, and acetone) and chlorinated solvents (e.g., from dichloromethane, dichloroethane, and chloroform);

for embodiment (2), in the case where two L groups together form the group-O-c (O) -O-or at least one L group is selected from-OH: aprotic solvents (e.g. from N-methyl-2-pyrrolidone, dimethylformamide and acetonitrile), and, although less preferably, water (preferably at a pH of 8.5 to 9.5, for example because it is used with a base such as ammonia);

for embodiment (4) aprotic solvents (e.g., from tetrahydrofuran, dimethoxyethane, and dioxane); and

for embodiment (5) aprotic solvents (e.g., from tetrahydrofuran, acetonitrile, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetone, and dioxane).

Step (i) may be effected at a temperature of greater than 40 ℃, preferably greater than 50 ℃, and more preferably at a temperature of 60-350 ℃. In some cases, the reaction is effected under reflux. However, in embodiment (4), the reaction may be effected at room temperature, for example at a temperature of at least 15 ℃ and preferably from 18 to 30 ℃.

Step (i) is typically carried out at ambient pressure (i.e. about 1 bar), although higher pressures may be used. For example, in embodiment (4), the reaction may be effected at a pressure greater than 2 bar, for example from 2 to 200 bar.

The reaction may be carried out for a period of time greater than 30 minutes, but preferably less than 6 hours and more preferably less than 4 hours. Longer reaction time periods may also be used, such as up to 48 hours or even longer.

In the case where two L groups together form the group-O-C (O) -O-or at least one L group is selected from-OH in embodiment (2), and in embodiment (4), for the preparation of intermediatescThe preferred process of (ii) comprises carrying out step (i) in the presence of a base. Suitable bases may be selected from:

inorganic bases, for example alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal alkoxides such as alkali metal tert-butoxide such as sodium tert-butoxide or potassium tert-butoxide, and alkali metal carbonates such as sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate and potassium carbonate, and

organic bases, for example nitrogen-containing organic bases, such as those from tetra-n-butylammonium fluoride, trimethylamine, diisopropylethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, pyridine and 4-dimethylaminopyridine.

The base is preferably an inorganic base, and more preferably a carbonate, especially potassium carbonate.

Relative to the starting materialsaThe base may be used in an amount of 0.005 to 0.3 molar equivalent, preferably 0.01 to 0.1 molar equivalent and more preferably 0.03 to 0.06 molar equivalent. It will be appreciated that these amounts mean that the base preferably acts as a catalyst and is no longer used as a reagent in the reaction. The reaction is generally effected in the absence of a metal catalyst.

In these embodiments, relative to the starting materialsaThe alkylating agent is generally used in an amount of 0.8 to 1.3 molar equivalents, preferably 0.9 to 1.1 molar equivalents and more preferably 1 to 1.02 molar equivalentsb. Thus, the number of the first and second electrodes,the alkylating agent may be effectively used in an amount just stoichiometric or slightly over stoichiometric. This is believed to enhance the intermediates obtainedcThe purity of (2).

In these embodiments, step (i) is preferably effected in the presence of a solvent. Step (i) may also be carried out in the absence of a solvent, although this is less preferred because of the intermediatecSpecial handling is required when not in a solvent.

The solvent is preferably a protic solvent. Protic solvents are well known in the art as solvents capable of donating protons. Protic solvents usually contain a hydrogen atom directly bound to nitrogen or oxygen.

Suitable protic solvents include water and alcohols. The alcohol may be selected from C_1-10Preferably C_3-8And more preferably C_5-6An alcohol. Preferred alcohols have formula C_nH_2n+1OH, although polyols such as diols and triols may also be used and have the formula C_nH_2n+2-m(OH)_mWherein m is preferably selected from 2 or 3 (e.g. ethylene glycol or propylene glycol). Preferably, the protic solvent is an alcohol, more preferably cyclohexanol or 4-methyl-2-pentanol.

It may be desirable to use a mixture of solvents, for example a mixture of two or more of the above mentioned protic solvents. This may be useful where it is desired to carry out the reaction in a particular solvent boiling range. For example, the reaction may be effected in the presence of two or more alcohols, for example selected from C_3-8Alcohol, and more preferably C_5-6An alcohol. In a particular embodiment, the reaction is effected in the presence of a mixture of isomers (e.g. a mixture of 4-methyl-2-pentanol and cyclohexanol).

Where mixtures of solvents are used, each solvent is preferably present in an amount of at least 10% and preferably at least 15% by total weight of the solvent system. For example, a mixture of 70-90% 4-methyl-2-pentanol and 10-30% cyclohexanol may be used.

May be used as per g of starting materialaThe solvent is used in an amount of 1.5 to 8 g, preferably 2 to 6 g and more preferably 2.5 to 4.0 g of solvent.

In these embodiments, the reaction may be effected at a temperature of at least 100 deg.C, for example at a temperature of 100-180 deg.C, preferably 110-160 deg.C, and more preferably at a temperature of 120-150 deg.C. In some cases, the reaction is effected under reflux.

In these embodiments, the reaction is typically effected at ambient pressure (i.e., about 1 bar).

In these embodiments, the reaction may be carried out for a period of time greater than 4 hours, but preferably less than 48 hours.

These embodiments are preferred because they are halogen-free. Particularly preferred alkylating agentsbThat is: wherein L and L' together form the group-O-C (O) -O-, i.e. an organic carbonate such as ethylene carbonate.

In step (ii) of the process, intermediatescPerforming a ring closure reaction to form a fuel additivee:

。

Step (ii) is preferably effected in the presence of a hydrogenation catalyst and a source of hydrogen. These conditions will reduce the nitro group to an amine, thereby allowing ring closure to occur.

The hydrogenation catalyst is preferably selected from palladium, platinum, nickel (e.g., raney nickel) and rhodium catalysts, although other metal catalysts such as vanadium may also be used. Preferred catalysts are generally selected from palladium and platinum catalysts, such as Pd/C, Pt (OH)₂And PtO₂. However, palladium and rhodium catalysts are particularly suitable in embodiment (1).

The source of hydrogen in step (ii) is preferably hydrogen, for example at a pressure of from 1 to 80 bar, preferably from 5 to 70 bar, and more preferably from 10 to 60 bar. Although less preferred, step (ii) may also be achieved using a source of hydrogen other than hydrogen, such as a hydride, for example sodium borohydride, sodium bis (2-methoxyethoxy) aluminum hydride (known as 'Red-Al'), lithium aluminum hydride, diisobutylaluminum hydride, lithium borohydride or zinc borohydride.

Step (ii) is preferably effected at a temperature of at least 20 ℃, for example at a temperature of 20-70 ℃, and preferably 25-60 ℃.

Preferably, step (ii) is effected in the presence of a protic solvent such as an alcohol (e.g. methanol or ethanol) or an organic acid (e.g. acetic acid, optionally in the presence of an inorganic acetate salt such as sodium acetate). These components are believed to maximize the activity of the catalyst.

Step (ii) is preferably effected in the presence of a reaction additive. Preferably, the reaction additive is an acid, such as an acid selected from inorganic acids such as hydrochloric acid and organic acids such as p-toluenesulfonic acid and acetic acid (acetic acid may also be used as a solvent). However, the reactive additive may also be ammonia, which is preferably used in combination with an alcohol such as methanol. Relative to the intermediatecPreferably, the ammonia is used in an amount of 2 to 4 molar equivalents. The use of ammonia as a reaction additive is particularly suitable for embodiment (1).

Step (ii) may also be effected in the presence of a catalyst other than those listed above, such as in the presence of sodium sulphide (e.g. preferably together with an alcoholic solvent such as ethanol) and an iron catalyst (preferably together with an organic acid solvent such as acetic acid).

The reaction in step (ii) may be carried out for a period of time greater than 1 hour, preferably greater than 2 hours. The reaction is typically effected for up to 24 hours.

In some embodiments, step (ii) is effected as a single reaction (i.e., using a set of reagents and under a set of conditions). However, in other embodiments, step (ii) comprises sub-steps.

Typically, in embodiments (1), (2) (except where two L groups together form the group-O-c (O) -O-or where at least one L group is selected from-OH), (3) and (6), step (ii) may be achieved as a single reaction. The intermediates of embodiment (1) are particularly suitable for single-step reduction and cyclization to form fuel additivese。

However, in embodiment (3), step (ii) may also comprise sub-steps. Preferably, the conditions of one of said sub-steps are as described above for step (ii) (i.e. the reaction is preferably carried out in the presence of a hydrogenation catalyst and a hydrogen source) and the other sub-step comprises hydrolysis of the acetal groupFor example, using an acid to form an aldehyde. In the case where hydrolysis is effected first, then the intermediate of embodiment (6) will be formedc. By reduction of the nitro group and hydrolysis of the acetal, then ring closure can occur.

The hydrolysis may be effected in the presence of an acid, for example a hydrogen halide such as HCl. Preferably, the acid is used as an aqueous acid. Suitable solvents for the hydrolysis reaction include aprotic solvents (e.g., acetone and acetonitrile). The hydrolysis may occur at a temperature of greater than 40 ℃, for example 40-90 ℃, and preferably 50-80 ℃. Hydrolysis typically occurs at room temperature. Hydrolysis may occur for more than 2 hours, for example 4 to 48 hours.

In embodiment (2) (where two L groups together form the group-O-c (O) -O-or where at least one L group is selected from-OH), (4) and (5), step (ii) preferably comprises sub-steps to increase the conversion of intermediate c to fuel additive e.

In which the intermediatecIn embodiments comprising a terminal hydroxyl group (i.e., embodiment (2) (wherein two L groups together form the group-O-c (O) -O-or at least one L group is selected from-OH) and embodiment (4)), step (ii) preferably comprises substeps (iia) and (iib), wherein the conditions of one of the substeps (iia) and (iib) are as described above for step (ii) (i.e., preferably the reaction is carried out in the presence of a hydrogenation catalyst and a hydrogen source), and the other substeps (iia) and (iib) comprise replacing the hydroxyl group in the substitution reaction with a leaving group L "selected from halogens (e.g., Cl, Br, I, preferably Cl or Br, and more preferably Br) and sulfonic acid esters (e.g., Br)-OSO₂A, wherein A is selected from tolyl, methyl, -CF₃、-CH₂Cl, phenyl and p-nitrophenyl). This promotes ring formation since halogen and sulfonate are better leaving groups than hydroxyl.

In the case where the substitution reaction is a halogenation reaction, it may be carried out in the presence of a hydrogen halide, preferably hydrogen bromide or hydrogen chloride. The hydrogen halide is preferably in the form of an aqueous solution.

Preferably a molar excess of hydrogen halide is used, for example by using at least 5: 1, preferably at least 10: 1 and more preferably at least 15: 1 of hydrogen halide with an intermediatecIn a molar ratio of (a).

The halogenation reaction can be carried out at a temperature greater than 60 ℃, preferably greater than 70 ℃ and more preferably greater than 80 ℃.

The substitution reaction is usually carried out at ambient pressure, i.e. about 1 bar.

The substitution reaction may be carried out for a period of time greater than 1 hour, preferably greater than 2 hours.

Alternatively, there may be a thionyl halide, a phosphorus tetrahalide, a phosphorus pentahalide, a phosphorus oxyhalide or a halogen gas (i.e., Br) in combination with a trialkylphosphine (e.g., trimethylphosphine) or a triarylphosphine (e.g., triphenylphosphine)₂、Cl₂Etc.) or in the presence of a carbon tetrahalide. In these embodiments, the halogenation reaction is preferably carried out in the presence of an aprotic solvent (e.g., tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, vinyl carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran (oxolane) or propionitrile and preferably a non-ether aprotic solvent such as dimethylformamide, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetone, dioxane, vinyl carbonate and acetonitrile) or a chlorinated solvent (e.g., dichloromethane, dichloroethane or trichloromethane).

For example, the halogenation reaction can be effected using the following reagents: thionyl halide in the presence of a chlorinated solvent (e.g., dichloromethane, dichloroethane or chloroform); in the presence of a triarylphosphine (e.g., triphenylphosphine) or a trialkylphosphine and preferably an aprotic solvent (e.g., acetonitrile) or a chlorinated solvent (e.g., dichloromethane), a halogen gas or a carbon tetrahalide; phosphorus trihalides, phosphorus pentahalides or phosphorus oxyhalides, preferably in the presence of an ammonium salt (e.g. a tetraalkylammonium halide such as tetrabutylammonium bromide); or an alkyl-or aryl-sulfonyl chloride (e.g., tosyl chloride or mesyl chloride), preferably in the presence of a trialkylamine (e.g., trimethylamine), and preferably in the presence of a chlorinated solvent (e.g., dichloromethane).

At the end ofIn the case where the hydroxyl group is substituted by a sulfonate group, HalOSO may be used₂A or ASO₂-O-SO₂A is effected in which Hal is halogen (preferably selected from Cl and Br) and A is selected from tolyl, methyl, -CF₃、-CH₂Cl, phenyl and p-nitrophenyl. Can be carried out in the presence of aprotic solvents (for example tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, vinyl carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran (oxolane) or propionitrile and preferably of aprotic solvents such as dimethylformamide, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, acetone, dioxane, vinyl carbonate or acetonitrile and preferably dimethylformamide, N-methyl-2-pyrrolidone, dimethylformamide, N-methylpyrrolidone, N-methyl-2-pyrrolidone, methyl-N-methyl-2-pyrrolidone, methyl, Dimethylacetamide, dimethylsulfoxide, acetone, dioxane, ethylene carbonate or acetonitrile) or chlorinated solvents (such as dichloromethane, dichloroethane or chloroform).

In case L "is a sulfonate, the substitution reaction preferably takes place in step (iia).

In which the intermediatecIn other particularly preferred embodiments comprising terminal hydroxyl groups, the ring closure reaction may occur by a two-step metal catalyzed mechanism, wherein the nitro group is first reduced to an amine in step (iia "), thereby allowing ring closure to occur in step (iib"):

。

the same metal catalyst may be used in the steps (iia ") and (iib") of the reaction, thereby enabling the reaction to be carried out in one pot.

At least step (iia ") is effected in the presence of a source of hydrogen. At least step (iib ") is carried out at a temperature of at least 100 ℃, and preferably in the presence of an aprotic solvent system.

The reaction is preferably effected as a one-step reaction, wherein the same reaction materials and preferably the same reaction conditions are used in steps (iia ") and (iib"). Thus, the reaction is preferably effected as a single step reaction, even if it is carried out by a two-step mechanism. In other less preferred embodiments, the reaction may be effected as a two-step reaction, wherein a first set of reaction materials and conditions is used to reduce the nitro group in step (iia ") and a second set of reaction materials and conditions is used to close the ring in step (iib").

One advantage of the metal-catalyzed ring-closure reaction is that it does not require the use of reagents in stoichiometric amounts. In a preferred embodiment, no other than intermediates are usedcAnd reagents other than a hydrogen source. Intermediates are consideredcAnd hydrogen sources are reagents because they are consumed during the reaction. Other components used in the reaction, such as metal catalysts, are not considered 'reagents' because they are not consumed during the reaction. In embodiments, the intermediates are referred tocIn an amount of at most 0.5 molar equivalent, preferably at most 0.3 molar equivalent and more preferably at most 0.2 molar equivalent except for the intermediatecA hydrogen source and an aprotic solvent system.

The metal-catalyzed ring-closure reaction is preferably effected in the absence of a halogen-containing reagent and an acidic reagent, preferably a strongly acidic reagent (i.e., a compound having a pH of less than 5 at 25 ℃ when present as a 0.01M aqueous solution of the compound).

Preferably, the intermediate is used only in the presence of the metal catalyst, the hydrogen source and the solvent systemcThe reaction is effected as a reagent, i.e. without the use of further reaction materials.

The preparation of fuel additives by metal catalysed reactions will now be described in detaileThe specific route of (1).

(1) One-step reaction

In a preferred embodiment, the reaction is preferably effected as a one-step reaction. Thus, the same reaction materials are used in steps (iia ") and (iib"), i.e. steps (iia ") and (iib") are effected in the presence of a metal catalyst, a hydrogen source and an aprotic solvent system.

It is to be understood that metal catalysts are catalysts containing a metal, and thus, they may contain a non-metallic element. Suitable metal catalysts for use in the one-step metal catalyzed reaction include those selected from palladium (e.g., Pd/C), nickel (e.g., in the presence of aluminum such as in Raney nickel or Ni-SiO₂/Al₂O₃Medium) and cobalt (e.g., in the presence of aluminum such as in raney cobalt) catalysts. Nickel catalyst, in particular Ni-SiO₂/Al₂O₃Is particularly preferred.

Relative to the intermediatecThe metal catalyst may be used in an amount of up to 0.3 molar equivalent, for example, 0.005 to 0.3 molar equivalent, preferably 0.01 to 0.25 molar equivalent, and more preferably 0.05 to 0.2 molar equivalent.

The reaction is also carried out in the presence of a source of hydrogen. The hydrogen source is preferably hydrogen, for example at a pressure of 1-50 bar, preferably 3-30 bar and more preferably 5-15 bar.

Although less preferred, a hydrogen transfer reagent may also be used as a source of hydrogen, such as formic acid, sodium formate or ammonium formate. The hydrogen transfer reagent will generate hydrogen gas in situ. The hydrogen transfer reagent may be used in conjunction with hydrogen gas, or as the sole source of hydrogen. The hydrogen transfer agent is preferably used in conjunction with a palladium catalyst such as Pd/C.

Relative to the intermediatecThe hydrogen transfer agent may be used in an amount of up to 5 molar equivalents, for example 0.1 to 5 molar equivalents, preferably 0.5 to 4 molar equivalents and more preferably 1 to 3 molar equivalents.

The one-step reaction is carried out in the presence of an aprotic solvent system. The aprotic solvent system is believed to facilitate the removal of water from the reaction mixture, particularly at reflux, which facilitates oxidative cyclization to occur.

It is to be understood that the aprotic solvent system is substantially free of any protic solvent, i.e. contains less than 2 vol.%, preferably less than 1 vol.% and more preferably less than 0.1 vol.% of protic solvent.

The aprotic solvent system preferably comprises an aromatic solvent, such as selected from toluene, benzene, xylene, trimethylbenzene, such as mesitylene, toluene, xylene, toluene, xylene, mesitylene, xylene,diphenyl ether, naphthalene, methyl-substituted naphthalenes (i.e., 1-or 2-methylnaphthalene), and anisole. Mesitylene is particularly suitable for one-step metal catalyzed reactions leading to fuel additiveseHigh yield of (a). Refinery streams containing mixtures of aromatics with suitable boiling ranges, for example falling in the range of 100-250 c, may also be used.

The aromatic solvent may be present in the aprotic solvent system in an amount of at least 30 wt.%, preferably at least 40 wt.% and more preferably at least 50 wt.%. In embodiments, the aromatic solvent is the only solvent used, i.e., the aprotic solvent system consists of an aromatic solvent.

The aprotic solvent system can also comprise a non-aromatic solvent. Preferred non-aromatic solvents are selected from heterocyclic solvents such as from tetrahydrofuran and 1, 4-dioxane. Other suitable aprotic non-aromatic solvents include dimethylacetamide. Preferably, non-aromatic solvents are used in combination with aromatic solvents.

In case the reaction is carried out as a one-step reaction, the reaction conditions are preferably the same in steps (iia ") and (iib"), i.e. steps (iia ") and (iib") are carried out at a temperature of at least 100 ℃. In some embodiments, pressure may be required to maintain the solvent system in the liquid phase at a temperature greater than 100 ℃. This may be the case where, for example, benzene or tetrahydrofuran is used. A suitable pressure may be reached by carrying out the reaction in the presence of hydrogen at the pressure given above, or other pressures may be applied which exceed the pressure given by hydrogen.

Preferably, steps (iia ") and (iib") are effected, for example, at temperatures of 100-. The one-step reaction is preferably effected under reflux.

In some embodiments, the method comprises a preheating step, which is effected before step (iia "). In the preheating step, the reactants may be brought to temperature over a period of up to 3 hours, preferably up to 2 hours, and more preferably up to 1.5 hours. The preheating step may be carried out at a temperature of 40-100 ℃.

The one-step reaction (i.e. steps (iia ") and (iib") together) may be carried out for a period of more than 2 hours, preferably more than 4 hours. Typically, a one-step reaction is achieved for up to 24 hours. These values do not include any time period in which the reaction mixture is preheated.

(2) Two-step reaction

The metal-catalyzed ring closure reaction can also be effected as a two-step reaction, in which different reaction materials and preferably different conditions are used in steps (iia ") and (iib"). Although different reaction materials may be used in steps (iia ") and (iib"), the same metal catalyst may be used throughout. This enables the reaction to be carried out as a one-pot reaction.

Suitable metal catalysts for use in the two-step, but preferably one-pot reaction include those selected from palladium (e.g. Pd/C), nickel (e.g. in the presence of aluminium such as Raney nickel or Ni-SiO₂/Al₂O₃Medium), cobalt (e.g., in the presence of aluminum such as in raney cobalt). Nickel catalysts, especially Raney nickel, and palladium catalysts, especially Pd/C, are particularly preferred.

Typically, all catalyst is added at the beginning of step (iia "). However, in some embodiments, it may be desirable to add some of the metal catalyst at the beginning of step (iia ") and to add the remainder of the metal catalyst at a later time in the reaction, for example at the beginning of step (iib"). In these embodiments, intermediates may be usedcHigher amounts of metal catalyst, for example from 0.005 to 0.3 molar equivalent, preferably from 0.01 to 0.25 molar equivalent and more preferably from 0.05 to 0.2 molar equivalent in step (iia "), and from 0.005 to 0.3 further molar equivalent, preferably from 0.01 to 0.25 further molar equivalent and more preferably from 0.05 to 0.2 further molar equivalent in step (iib").

A step (iia ") of carrying out a two-step reaction in the presence of a source of hydrogen. The hydrogen source is preferably hydrogen, for example at a pressure of 1-50 bar, preferably 3-30 bar and more preferably 5-15 bar.

The step (iib ") of the two-step reaction may also be effected in the presence of a source of hydrogen, for example as described in relation to step (iia"). For example, step (iib ") may be carried out in the presence of the same source of hydrogen as step (iia"). However, step (iib ") may also be carried out in the absence of a hydrogen source. For example, the reaction chamber may be vented to remove any hydrogen prior to step (iib "). In this case, step (iib ") is preferably carried out at ambient pressure (i.e. at a pressure of about 1 bar).

The step of the two-step reaction (iib ") is preferably carried out in the presence of an aprotic solvent system. The aprotic solvent system is believed to facilitate the removal of water from the reaction mixture, particularly at reflux, which facilitates oxidative cyclization to occur.

The aprotic solvent system preferably comprises an aromatic solvent, such as a solvent selected from toluene, benzene, xylene, trimethylbenzenes such as mesitylene, diphenyl ether, naphthalene, methyl-substituted naphthalenes and anisoles. Mesitylene is particularly suitable for the process of the invention, resulting in a fuel additiveeHigh yield of (a). Refinery streams containing mixtures of aromatics with suitable boiling ranges, for example falling in the range of 100-250 c, may also be used.

The aprotic solvent system can also comprise a non-aromatic solvent. Preferred non-aromatic solvents are selected from heterocyclic solvents such as from tetrahydrofuran and 1, 4-dioxane. Preferably, non-aromatic solvents are used in combination with aromatic solvents.

The step (iia ") of the two-step reaction is preferably also effected in the presence of an aprotic solvent system (e.g. as described above), since this is believed to result in a higher yield. However, it may also be effected in the presence of a protic solvent system, such as an aqueous (i.e. aqueous) solvent system or an alcoholic solvent system (e.g. methanol or ethanol).

In case the reaction is carried out as a two-step reaction, the reaction conditions are preferably different in steps (iia ") and (iib"). Step (iib ") is effected at a temperature of at least 100 ℃. As mentioned above, pressure may be required to maintain the solvent system in the liquid phase at a temperature greater than 100 ℃. A suitable pressure may be reached by carrying out the reaction in the presence of hydrogen at the pressure given above, or other pressures may be applied which exceed the pressure given by hydrogen.

Preferably step (iib) is effected at a temperature of, for example, 100-. Step (iib ") is preferably carried out under reflux.

However, step (iia ") is preferably effected at a lower temperature than step (iib"). For example, step (iia) may be effected at a temperature of 10-100 ℃, preferably 15-80 ℃ and more preferably 20-60 ℃.

The two-step reaction (i.e. steps (iia ") and (iib") together) may be carried out for a period of more than 2 hours, preferably more than 10 hours. Step (iia ") is preferably effected for a period of more than 1 hour. Preferably step (iib ") is effected for a period of more than 8 hours. Typically, a two-step reaction (i.e. steps (iia ") and (iib") together) is effected for up to 48 hours.

In embodiment (5), intermediatescContaining terminal acid or ester groups. In these embodiments, step (ii) preferably comprises the following sub-steps:

。

substep (iia')The conditions of (a) are as described above in relation to step (ii), i.e. the reaction is preferably carried out in the presence of a hydrogenation catalyst and a hydrogen source. This results in amide containing intermediatesdIs performed. Substep (iib') involves reducing the amide to the amine.

The reduction of the amide to the amine can be accomplished in the presence of a reducing agent or using catalytic reduction.

Preferred reducing agents for use in substep (iib ') are selected from sodium bis (2-methoxyethoxy) aluminum hydride (referred to as ' Red-Al '), lithium aluminum hydride, borane, preferably in combination with dimethyl sulfide, diisobutylaluminum hydride and borohydride. Suitable borohydrides include: sodium borohydride, preferably in combination with boron trifluoride etherate, iodine, titanium tetrachloride, cobalt (II) chloride or acetic acid; lithium borohydride, preferably in combination with trimethylsilyl chloride; and zinc borohydride.

In the case of Red-Al, this is preferably combined with an alkali metal halide such as potassium fluoride. Can be used as an intermediatedThe alkali metal halide is used in an amount of 0.1 to 1%, preferably 0.2 to 0.6% by weight of (A).

The reducing agent may be added dropwise to the reaction mixture, for example over a period of at least 2 hours, preferably at least 3 hours and more preferably at least 4 hours.

Relative to the intermediatedThe reducing agent may be used in substep (iib') in an amount of 1 to 4 molar equivalents, preferably 1.5 to 3 molar equivalents and more preferably 1.75 to 2.25 molar equivalents.

It is preferable to use an aprotic solvent such as an aprotic solvent selected from the group consisting of tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, ethylene carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran (oxolane) and propionitrile together with a reducing agent, and toluene, tetrahydrofuran, dimethoxyethane and dioxane are preferable. In some embodiments, tetrahydrofuran is preferred for use as an aprotic solvent.

Relative to the intermediatedThe aprotic solvent may be used in step (iib') in an amount of 4 to 20 equivalents, preferably 6 to 16 equivalents and more preferably 8 to 12 equivalent weight.

Preferred combinations of reducing agents/solvents are as follows:

Red-Al/toluene

Lithium aluminium hydride/tetrahydrofuran or dimethoxyethane or dioxane

Borane in combination with dimethylsulfide/tetrahydrofuran

Diisobutylaluminum hydride/tetrahydrofuran

Sodium borohydride, boron trifluoride diethyl etherate/tetrahydrofuran

Sodium borohydride, iodine/tetrahydrofuran

Lithium borohydride, trimethylsilyl chloride/tetrahydrofuran

Sodium borohydride, titanium tetrachloride/dimethoxyethane

Zinc borohydride/tetrahydrofuran

Sodium borohydride, cobalt (II) chloride/tetrahydrofuran

Sodium borohydride, acetic acid/dioxane.

If step (iib') is carried out in the presence of a reducing agent, it is preferably carried out at ambient temperature, i.e. at a temperature of from 15 to 25 ℃. Since the reaction may be exothermic, the reaction mixture may need to be cooled to maintain the temperature in this range. In other embodiments, the reaction may be cooled, for example, to a temperature of less than 15 ℃, such as 0-10 ℃.

The reaction is preferably effected at ambient pressure, i.e. a pressure of about 1 bar.

If step (iib') is carried out in the presence of a reducing agent, the reaction may be quenched using a base, preferably an inorganic base such as an alkali metal hydroxide. Sodium hydroxide and potassium hydroxide are preferred, especially sodium hydroxide.

The base for quenching may be added dropwise over a period of at least 30 minutes, preferably at least 1 hour and more preferably at least 2 hours.

In case catalytic reduction is used to achieve the substep (iib'), it may be carried out in the presence of hydrogen at a pressure of from 1 to 80 bar, preferably from 3 to 60 bar and more preferably from 5 to 50 bar.

Suitable catalysts for substep (iib') include ruthenium, platinum, palladium, and rhodium catalysts, with ruthenium catalysts such as ruthenium (III) acetylacetonate being preferred.

In certain particularly preferred embodiments, the ruthenium hydrogenation catalyst may be formed in situ from a mixture of ruthenium (III) acetylacetonate, triphos (e.g., 1,1, 1-tris (diphenylphosphinomethyl) ethane), and ytterbium (III) trifluoromethanesulfonate, preferably in the presence of methanesulfonic acid and trifluoromethanesulfonimide.

Relative to the intermediatedThe catalyst may be used in an amount of less than 1 molar equivalent, preferably less than 0.5 molar equivalent and more preferably less than 0.1 molar equivalent.

In the case of step (iib') being carried out using catalytic reduction, it is preferable to use, together with the catalyst, an aprotic solvent such as an aprotic solvent selected from tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, ethylene carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran (oxolane) and propionitrile. The aprotic solvent is preferably tetrahydrofuran.

In case step (iib') is achieved using catalytic reduction, the reaction may be carried out at a temperature of more than 80 ℃, preferably more than 100 ℃ and more preferably more than 120 ℃.

The reaction in step (iib') is preferably carried out for at least 2 hours, preferably at least 5 hours and more preferably at least 10 hours.

In a very specific embodiment, step (iib') is carried out in the presence of a reducing agent (e.g., Red-Al), a solvent (e.g., toluene), and at a temperature of 10 to 20 ℃. The reaction is quenched with a base (e.g., sodium hydroxide).

In another very specific embodiment, step (iib') is carried out in the presence of a reducing agent (e.g., lithium aluminum hydride), a solvent (e.g., tetrahydrofuran), and at a temperature maintained below 10 ℃.

In another very specific embodiment, step (iib') is carried out in the presence of a reducing agent (e.g., borane), a solvent (e.g., tetrahydrofuran), and at a temperature of 0-5 ℃.

In other embodiments where step (iib') is achieved using catalytic reduction, it may be achieved in the absence of hydrogen, for example hydrogen is present at a level of less than 10 ppm and preferably less than 1 ppm by volume. In these embodiments, the reaction is effected in the presence of a source of silane hydrogen. Suitable silanes include alkoxysilanes (e.g., (EtO)₃SiH) and aryl silanes (e.g. PhSiH)₃)。

Preferred catalysts for carrying out the reaction in the absence of hydrogen are selected from metal catalysts. Preferably, the catalyst is selected from ruthenium and zinc catalysts. Relative to the intermediatedThe catalyst may be used in an amount of up to 0.5 molar equivalents, preferably 0.01 to 0.15 molar equivalents.

If step (iib ') is effected using catalytic reduction but is carried out in the absence of hydrogen, preferably in the presence of a solvent, preferably selected from aprotic solvents such as those listed previously for step (iib'), and preferably tetrahydrofuran.

If step (iib ') is achieved using catalytic reduction but in the absence of hydrogen, step (iib') may be carried out at a temperature of greater than 10 ℃, preferably from 15 to 50 ℃ and more preferably from 20 to 40 ℃.

If step (iib ') is achieved using catalytic reduction but in the absence of hydrogen, step (iib') may be performed at ambient pressure (i.e., about 1 bar). The reaction may be carried out under an inert atmosphere, for example under argon.

If step (iib') is achieved using catalytic reduction but in the absence of hydrogen, the reaction may be carried out for a period of time greater than 20 minutes, preferably greater than 1 hour, but preferably less than 24 hours.

The process of the invention is preferably carried out on an industrial scale. For example, in the preparation of fuel additiveseThe process is a batch processIn this case, the fuel additive is preferably produced in a batch quantity of more than 100kg, preferably more than 150kg, and more preferably more than 200kge. The process can also be carried out as a continuous process.

In order to produce the fuel additive on an industrial scale, steps (i) and (ii) are preferably carried out in a reactor having a volume of at least 500L, preferably at least 750L and more preferably at least 1000L. It will be appreciated that steps (i) and (ii) may be carried out in the same reactor.

eOctane enhancing fuel additive

Fuel additives prepared using the process of the inventioneHaving the formula:

wherein: r₁Is hydrogen;

n is 0 or 1.

Preferred substituents for fuel additives are described below. It will be appreciated that the preferred substitution patterns also apply to the preparation of fuel additives therefromeOf (2) a starting materialaReagent for the preparation of the samebAnd intermediatesc、d and d'。

In some embodiments, R₂、R₃、R₄、R₅、R₁₁And R₁₂Each independently selected from hydrogen and alkyl, and preferably from hydrogen, methyl, ethyl, propyl and butyl. More preferably, R₂、R₃、R₄、R₅、R₁₁And R₁₂Each independently selected from hydrogen, methyl and ethyl, and even more preferably from hydrogen and methyl.

In some embodiments, R₆、R₇、R₈And R₉Each independently selected from hydrogen, alkyl and alkoxy and preferably from hydrogen, methyl, ethyl, propyl, butyl, methoxy, ethoxy and propoxy. More preferably, R₆、R₇、R₈And R₉Each independently selected from hydrogen, methyl, ethyl and methoxy and even more preferably from hydrogen, methyl and methoxy.

Advantageously, R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂And preferably R₆、R₇、R₈And R₉At least one of which is selected from groups other than hydrogen. More preferably, R₇And R₈At least one of which is selected from groups other than hydrogen. In other words, the octane enhancing additive consists of R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂At least one of the positions represented, preferably at the position represented by R₆、R₇、R₈And R₉At least one of the positions represented by R, and more preferably at least one of the positions represented by R₇And R₈At least one of the represented positions may be substituted. It is believed that the presence of at least one group other than hydrogen may improve the solubility of the octane boosting additive in the fuel.

Also advantageously, R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂No more than five of (a), preferably no more than three, and more preferably no more than two, are selected from groups other than hydrogen. Preferably, R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂One or both of which are selected from groups other than hydrogen. In some embodiments, R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂Only one of which is selected from groups other than hydrogen.

Also preferred is R₂And R₃Is hydrogen, and more preferably R₂And R₃Both are hydrogen.

In a preferred embodiment, R₄、R₅、R₇And R₈At least one of which is selected from methyl, ethyl, propyl and butyl and R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂The remainder of (a) is hydrogen. More preferably, R₇And R₈Is selected from methyl, ethyl, propyl and butyl, and R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂The remainder of (a) is hydrogen.

In a further preferred embodiment, R₄、R₅、R₇And R₈Is methyl, and R is₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂The remainder of (a) is hydrogen. More preferably, R₇And R₈At least one of which is methyl and R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₁And R₁₂The remainder of (a) is hydrogen.

Preferably, X is-O-or-NR₁₀-, wherein R₁₀Selected from hydrogen, methyl, ethyl, propyl and butyl, and preferably from hydrogen, methyl and ethyl. More preferably, R₁₀Is hydrogen. In a preferred embodiment, X is-O-.

n may be 0 or 1, although preferably n is 0.

Octane boosting additives that may be used in the present invention include:

。

preferred octane boosting additives include:

。

particularly preferred are octane boosting additives:

。

fuel additives may be used in the fuel compositioneA mixture of (a). For example, the fuel composition may comprise a mixture of:

。

it is understood that reference to alkyl groups includes the different isomers of alkyl groups. For example, reference to propyl includes n-propyl and isopropyl, and reference to butyl includes n-butyl, isobutyl, sec-butyl and tert-butyl.

Additive and fuel composition

The present invention provides a fuel additive obtainable by the process of the inventione. Preferably, the fuel additive is obtained by the process of the present invention.

The present invention also provides a method for preparing a fuel for a spark-ignition internal combustion engine, the method comprising:

preparation of Fuel additives Using the Process of the inventione(ii) a And

the fuel additive is blended with a base fuel.

Fuel for a spark-ignited internal combustion engine is also provided. The fuel comprises a fuel additive obtainable and preferably obtained by the process of the inventioneAnd a base fuel.

Gasoline fuels (including those containing oxygenates) are commonly used in spark-ignited internal combustion engines. Accordingly, the fuel composition that may be prepared according to the process of the present invention may be a gasoline fuel composition.

The fuel composition may comprise a major amount (i.e. more than 50 wt%) of a liquid fuel ("base fuel") and a minor amount (i.e. less than 50 wt%) of a fuel additive composition of the present invention. Examples of suitable liquid fuels include hydrocarbon fuels, oxygenate fuels, and combinations thereof.

The fuel composition may contain an octane boosting fuel additive in an amount of up to 20%, preferably from 0.1% to 10% and more preferably from 0.2% to 5% of additive weight per weight of base fuele. Even more preferably, the fuel composition contains the fuel additive in an amount of from 0.25% to 2% and even more preferably still from 0.3% to 1% additive weight/base fuel weight. It should be understood that when more than one octane boosting fuel additive is usedeThese values refer to the total amount of octane boosting additive described herein in the fuel.

The fuel composition may comprise at least one other fuel additive. Examples of such other additives that may be present in the fuel composition include detergents, friction modifiers/antiwear additives, corrosion inhibitors, combustion modifiers, antioxidants, valve seat recession additives, dehazers/demulsifiers, dyes, markers, fragrances, antistatic agents, biocides, and lubricity improvers. It is also possible to use additional octane improvers in the fuel composition, i.e. without octane boosting fuel additiveseThe octane improver of (1).

The fuel composition is used in a spark-ignition internal combustion engine. Examples of the spark ignition internal combustion engine include a direct injection spark ignition engine and a port fuel injection spark ignition engine. Spark ignition internal combustion engines may be used in automotive applications, such as in vehicles such as passenger cars.

The invention will now be described with reference to the following non-limiting examples.

Examples

eExample 1 preparation of Fuel additive according to embodiment (1)

In step (i), a plurality of reagents are usedbPreparation of the following intermediatesc:

。

In the first experiment, bromonitrile was used as a reagentb. Specifically, 2-nitrophenol (10.0 g, 72mmol), bromoacetonitrile (0.9 eq.), and K₂CO₃(2 eq) was refluxed in acetonitrile for 20 h. The solvent was evaporated and the residue partitioned between water and ethyl acetate, the organic layer was washed with K₂CO₃The aqueous solution was washed 3 times. The organic phase was dried over sodium sulfate, the solvent was removed in vacuo and the residue was triturated with hexanes to give 11.1 g (86% yield) of intermediate as a pale green solidc。

In a second experiment, chloronitrile was used as a reagentb. Specifically, 2-nitrophenol (10.0 g, 72mmol), chloroacetonitrile (0.9 eq.) and K₂CO₃(2 eq) was refluxed in acetonitrile for 20 h. The solvent was evaporated and the residue was partitioned between water and ethyl acetate. The organic layer is treated with K₂CO₃The aqueous solution was washed 3 times. The organic phase was dried over sodium sulfate, the solvent was removed in vacuo and the residue was triturated with hexanes to give 6.8 g (53% yield) of intermediate as a brown solidc。

In a third experiment, 2- [ [ (4-methylphenyl) sulfonyl ] was used]Oxy radical]Acetonitrile as reagentb. Specifically, 2-nitrophenol (10.0 g)72mmol), 2- [ [ (4-methylphenyl) sulfonyl group]Oxy radical]Acetonitrile (0.9 eq.) and K₂CO₃(2 eq) was refluxed in acetonitrile for 20 h. The solvent was evaporated and the residue was partitioned between water and ethyl acetate. The organic layer is treated with K₂CO₃The aqueous solution was washed 3 times. The organic phase was dried over sodium sulfate, the solvent was removed in vacuo and the residue was triturated with hexanes to give 10.3g (80% yield) of intermediate as a light brown solidc。

In an alternative step (i), the following intermediates were prepared.

Using 4-methyl-2-nitrophenol as starting materialaAnd using chloroacetonitrile as reagentb. Specifically, 4-methyl-2-nitrophenol (60.0 g), chloroacetonitrile (1.4 equivalents), NaI (0.05 equivalents), and K₂CO₃(1.2 eq.) was heated in acetone (8 vol.) at 60 ℃ for 20 hours. Recrystallizing the product to produce an intermediatec82% yield.

In step (ii), the intermediate is reacted with a catalystcReduction and cyclization to produce the following fuel additivese：

。

Concretely, 2- (2-nitrophenoxy) acetonitrile (2.0 g, 11 mmol),pTSA (50 mg), 10% Pd/C (100mg) in ethanol (35 ml) at 50 bar H₂Stirring was continued at 50 ℃ for 2 hours. The reaction mixture was filtered, the solvent was evaporated, the residue was dissolved in ether and filtered to remove the solid. The solvent was removed in vacuo to yield 1.34 g (88% yield) of the fuel additive as a clear brown oile。

In an alternative step (ii), the following fuel additives were preparede：

。

Specifically, the intermediate isc(2.0 g、11 mmol)、NH₃Solution in MeOH, 5% Pd/C (1-2 mol%) in ethanol at 10 bar H₂Stirring was continued at 50 ℃ for 20 hours. Although H₂The pressure is lower, and the fuel additive is still obtainedeAbout 68% yield.

A similar experiment was performed, in which: using a platinum catalyst instead of a palladium catalyst; use ofpTSA as a reaction additive to replace NH₃A solution in MeOH; use of HCl as a reaction additive to replace NH₃A solution in MeOH; or no reactive additives. And use of NH₃Each of these reactions produced fuel additives in good but lower yields than those obtained with solutions in MeOHe。

Using NH₃Further experiments were carried out with a solution in MeOH as reaction additive. Experiments show that the intermediate is relativelycThe yield is highest in the case of using ammonia in an amount of 2 to 4 molar equivalents. The advantageous effect of using ammonia as a reaction additive was observed using palladium and rhodium catalysts. Experiments also show that it is preferred to carry out the reaction in the absence of water. Temperatures below 70 ℃ also give better yields. Experiments have shown that the use of rhodium catalysts gives slightly higher yields compared to palladium catalysts, whereas the use of vanadium and nickel catalysts reduces yields.

eExample 2 preparation of Fuel additive according to embodiment (2)

In step (i), a plurality of reagents are usedbThe following intermediates were preparedc:

。

In the first experiment, chlorobromoethane was used as reagentb. Specifically, 2-nitrophenol (5.0 g), chlorobromoethane (4 equivalents), and K₂CO₃The mixture (2 eq) was heated at reflux in MeCN (100 ml) for 2.5 h, the solvent was evaporated and partitioned between ethyl acetate and water. Passing the organic phase throughDried over sodium sulfate, the solvent was evaporated and the residue was triturated with hexanes to give 6.8 g (94% yield) of intermediate as a pale yellow solidc。

In a second experiment, dibromoethane was used as reagentb. Specifically, 2-nitrophenol (10.0 g, 72mmol), dibromoethane (5 equivalents) and K₂CO₃The mixture (2 eq) was refluxed in acetonitrile (200 ml) for 2 hours. The reaction mixture was partitioned between water and diethyl ether, the organic layer was dried over sodium sulfate, evaporated and redissolved in a small amount of diethyl ether. Insoluble material was removed and the organic solvent was evaporated to give 15.8 g (89% yield) of intermediate as a yellow oilc。

In a third experiment, 2-bromoethanol was used as reagentb. Specifically, 2-nitrophenol (10 g, 72mmol), 2-bromoethanol (4 equivalents), and K₂CO₃(2.0 equiv.) the mixture was refluxed in MeCN (75 ml) for 4 h, the organic solvent was evaporated, the residue was partitioned between ether and water, the organic layer was separated, washed with water, dried over sodium sulfate and the solvent was evaporated in vacuo. The residue was purified by column chromatography (1:1 ethyl acetate/hexane) and 10.2 g (77% yield) were obtained as intermediate for a yellow oilc。

In an alternative step (i), the following intermediates were preparedc：

。

Using 4-methyl-2-nitrophenol as starting materialaAnd using ethylene carbonate as reagentb. Mixing the starting materialsa(100 g, 0.653 mol), reagentsb(1 eq) and potassium carbonate (0.04 eq) in 4-methyl-2-pentanol (400 mL) were heated at reflux (137 ℃ C.) for 37 hours. HPLC analysis of the reaction mixture confirmed the materialc92% conversion and 89% selectivity.

。

In a first experiment, the intermediate in ethyl acetate (100 ml) was usedc(wherein L is Cl) (6.0 g, 30mmol), PtO₂(50 mg) and sodium acetate (1 eq.) at 10 bar and 25 ℃ for 2 h. The reaction mixture was filtered and the resulting red oil was extracted in ethyl acetate and Et was added₃N (1 eq) and NaI (200 mg) and the mixture was refluxed for 16 hours to give the fuel additive in 37% yielde。

In a second experiment, the intermediate in ethyl acetate (30 ml) was usedc(where L is Br) (3.0 g, 12.2mmol), sodium acetate (1 eq.) and Pt₂O (10 mg) was hydrogenated at 10 bar and 25 ℃ for 18 h. The mixture was filtered and the brown oil was dissolved in ethyl acetate (25 ml) and Et₃N (2 ml) and refluxed for 6 hours to yield a fuel additive containing 80% of the fuel additiveeProduct of (use)¹H-NMR).

In an alternative step (ii), the following reaction is carried out:

。

screening work was performed to determine if a one-pot reaction was feasible. The following conditions were demonstrated to produce fuel additives in promising yieldse：

。

After successful results with Pd/C, different nickel (Lanni-Ni and Ni-SiO) were used₂/Al₂O₃) The same conversion was performed with a cobalt (Raney-Co) catalyst.

Making the intermediatec(1.97 g, 10 mmol, 0.05M) in THF/toluene (200 mL, 1:1) at 135 deg.C, 2 bar H₂And passed through the catalyst bed at a rate of 1 mL/min. After about 6-8 hours of continuous circulation of the eluent stream, GC analysis indicated intermediatescComplete conversion of (2). Observe the middleBodycProduced a fuel additive in each experimente. Higher yields were obtained when raney-Ni and raney-Co were used.

Further experiments were conducted using different nickel catalysts in a mesitylene solvent system. Two nickel catalysts were tested: Raney-Ni (in the form of a slurry in water) and Ni (65% by weight)/SiO₂/Al₂O₃(20 mg，10 mol%)。

The catalyst was charged to an argon purged stainless steel autoclave (300 mL). Adding the intermediate theretoc(394mg, 2.0 mmol) followed by addition of mesitylene (10 mL). The autoclave was sealed, charged with hydrogen to 7 bar and heated to 50 ℃ for 1 hour, then the temperature was raised to 170 ℃. The reaction was held at this temperature for 20 hours, then cooled to room temperature and sampled for uplc (mecn) analysis. LC analysis indicating intermediatecFor Raney-Ni and Ni-SiO₂/Al₂O₃Catalyst to produce fuel additive separatelye83% and 87% yield.

A further one-pot experiment was performed to investigate the use of different reaction materials and conditions in steps (iia ") and (iib"). The intermediate used in example 1 was used in these experimentscThe same compound of (1).

The following reaction materials and conditions were used:

¹ a one-step reaction, but wherein different reaction conditions are used in steps (iia ") and (iib").

If the solvent is changed between steps (iia ") and (iib"), the original solvent is removed by distillation. If hydrogen is removed after step (iia "), this is achieved by simply venting the reaction environment.

In each experiment, a fuel additive was producede。The best yields are obtained when aprotic solvents, in particular mesitylene, are used in steps (iia ") and (iib"). When extra is added in step (iib ″)Improved yields are also obtained with the catalyst.

eExample 3 preparation of Fuel additive according to embodiment (3)

In step (i), the following intermediates were preparedc:

。

Using bromoacetaldehyde diethyl acetal as reagentb. Specifically, 2-nitrophenol (5.0 g, 36 mmol), bromoacetaldehyde diethyl acetal (1 eq.) and K₂CO₃(1 eq) the mixture was heated to 120 ℃ in NMP (30 ml) for 16 hours, then cooled to ambient temperature and K was added₂CO₃Aqueous solution and extracted into ether. The organic phase is treated with K₂CO₃The aqueous solution was washed 3 times, dried over sodium sulfate and evaporated in vacuo to yield 8.5 g (92% yield) of intermediate as an orange oilc。

In an alternative step (i), the following intermediate c was prepared:

。

use of chloroacetaldehyde dimethanol as reagentb. Specifically, 4-methyl-2-nitrophenol (20.0 g), chloroacetaldehyde dimethanol (1.3 equivalents), NaI (0.1 equivalent), and K₂CO₃(1.1 equiv.) the mixture was heated to 110-150 ℃ in NMP (4 vol.) for 3 days to produce a crude intermediatec97% yield. A similar experiment was successfully performed in which DMF was used as the solvent instead of NMP. In the absence of K₂CO₃In the presence and absence of K₂CO₃And NaI, other similar experiments were also successfully performed.

。

Specifically, the intermediate isc(2.0 g, 8 mmol), 10% Pd/C (100mg) and pTSA (50 mg) were hydrogenated in dioxane (30 ml) at 30 bar at 25 ℃ for 2 h and then the temperature was raised to 100 ℃ and maintained at that temperature overnight. TLC analysis of the reaction mixture confirmed the reduction of the nitro group to the amino group, but minimal cyclization was observed. 1 ml of concentrated HCl was added and hydrogenated at 50 ℃ and 40 bar for 2 hours. Sampling confirmed that no acetal remained in the reaction, so it was filtered and diluted with water to give a pink solid. TLC analysis indicated the presence of fuel additiveeOf impure mixtures of。

In an alternative step (ii), intermediates from alternative step (i) are addedcConversion to the following compounds:

i.e., the intermediate of embodiment (6)c。

Specifically, in the first experiment, the intermediate was usedcHydrolysis was carried out at 50 ℃ for 43 hours in acetone/HCl. Intermediate to embodiment (6) was observedcGood transformation of (2). In a second experiment, the intermediate was addedcHydrolysis was carried out at 65 ℃ in a mixture of acetonitrile (8 vol), water (12 vol) and HCl (37% solution, 0.5 eq). After 27 hours, 99% conversion was observed. The intermediate of embodiment (5) can then be hydrogenatedcConversion to fuel additivese。

In a further alternative step (ii), intermediates from alternative step (i) are addedcReduction to form the following intermediate products:

。

specifically, the intermediate was reacted in the presence of 5% Pd/C (0.5 mol%)c(2.0 g) at 10 bar H₂The reaction mixture was hydrogenated in ethanol (15 vol.) at 50 ℃ for 8 hours. Complete conversion of the nitro group to the amine was observed to yield a very clean intermediate. Then can pass throughHydrolysis and subsequent ring closure to convert intermediates to fuel additivese。

e Example 4 preparation of Fuel additive according to embodiment (5)

The following intermediates were prepared by reacting 5-methyl-2-nitrophenol with chloroacetic acid, followed by amide reduction to amine and acid catalyzed ring closured:

。

Intermediates are prepared using a number of different methodsdConversion to the following Fuel additivese：

。

In a first experiment, 70% w/w sodium bis (2-methoxyethoxy) aluminum hydride in toluene (461 kg, 1596 mol, 2.05 eq.) was added to the intermediate over 6.5 hours while maintaining the temperature at 20. + -. 2 ℃d(127 kg, 778 mol, KF 0.04%), toluene (1101 kg, 10 equivalent volumes). The resulting clear red-orange solution was maintained at 20 ± 2 ℃ for 24 hours and then sampled for analysis. HPLC analysis of the product indicated 99.75% conversion with 81.9% fuel additivee. The reaction mixture was quenched with NaOH and extracted with toluene. The toluene solution was washed 3 times with water, the solvent was evaporated and the residue was purified by vacuum distillation to yield 158 kg (85.3% yield) of the fuel additivee。

In a second experiment, lithium aluminum hydride pellets (76.65 g, 1.6 equiv.) were stirred under nitrogen in THF (2.5L) and then cooled to<10 ℃. The intermediate is reacted with a catalystd(206 g) Adding the mixture into lithium aluminum hydride slurry in portions while maintaining the temperature<10 ℃. The reaction mixture was stirred at room temperature for 16 hours. The mixture was quenched with water, 15% aqueous NaOH was added, and the slurry was stirred for 16 hours, filtered and extracted with EtOAc. The organic solvent was evaporated to a brown oil, which was distilled (120 ℃, 0.05 mmHg) to yield 175 g (93%) of fuel additivee。

In a third method, an intermediate is introducedd(10 g, 61 mmol) was suspended in dry THF (80 ml), the slurry was cooled to 0-5 deg.C and BH was added₃THF (1.5 equivalents). The reaction mixture was warmed to ambient temperature and then heated to 60 ℃ for 16 hours and quenched with methanol and 1M aqueous HCl. The solvent was evaporated, the residue basified with NaOH and extracted into ether. The ether phase was washed 2 times with water, dried over magnesium sulfate and the solvent was evaporated to yield 9 g (99%) of the fuel additive as a yellow oile。

cExample 5 preparation of intermediate according to embodiment (6)

In step (i), the following intermediate c was prepared:

。

using chloroacetaldehyde as reagentb. Specifically, 2-nitrophenol (10.0 g, 72mmol), chloroacetaldehyde in water (50%) (2 equiv.), NaHCO₃(1.1 equiv.), KBr (0.12 equiv.), and NMeBu₃Cl (0.02 eq) was stirred in toluene (50ml) and water (20 ml) at 65 ℃ for 3 h. TLC analysis indicated a complex mixture in which the intermediate was presentc。

The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Rather, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed in the form of "40 mm" is intended to mean "about 40 mm".

Each document cited herein, including any cross referenced or related patent or application, is hereby incorporated by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it teaches, suggests or discloses any such invention alone or in any combination with any other reference or references. In addition, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope and spirit of this invention.

Claims

1. A process for preparing a fuel additive having the formulaeThe method of (1):

wherein: r₁Is hydrogen;

n is a number of 0 or 1,

the method comprises effecting the following reaction:

(i) adding an alkylating agent b to the starting materiala：

To form an intermediatec(ii) a And

(ii) making the intermediatecClosed-loop to form fuel additivese，

Wherein alkylating agent b and intermediate c are selected from:

R₁₄selected from hydrogen and alkyl.

2. The process according to claim 1, wherein step (i) is effected in the presence of a base, preferably selected from:

inorganic bases, for example from alkali metal hydroxides (such as sodium hydroxide and potassium hydroxide) and carbonates (such as sodium bicarbonate, sodium carbonate, potassium bicarbonate and potassium carbonate), and

organic bases, for example from nitrogen-containing organic bases, such as from trimethylamine, diisopropylethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, pyridine and 4-dimethylaminopyridine.

3. The process according to claim 1 or 2, wherein step (i) is effected in the presence of a catalyst, wherein the catalyst is preferably selected from the group consisting of acids (e.g. p-toluenesulfonic acid or sodium bisulfite), zeolites (e.g. zeolite Y, sodium (faujasite)), metal catalysts (e.g. palladium catalysts, preferably used with a zinc oxide support), halogen exchange catalysts (e.g. alkali metal halides such as KBr, NaBr, KI and NaI) and phase transfer catalysts (e.g. quaternary ammonium salts such as tetraalkylammonium halides, preferably butyltriethylammonium chloride or methyltributylammonium chloride).

4. The process according to any one of claims 1-3, wherein step (i) is effected in the presence of a solvent selected from aprotic solvents (e.g. selected from tetrahydrofuran, acetonitrile, dimethoxyethane, dioxane, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, ethylene carbonate, sulfolane, diphenyl ether, acetonitrile, 2-nitropropane, acetone, butan-2-one, butyl formate, ethyl acetate, isobutyronitrile, methyl acetate, methyl formate, nitromethane, tetrahydrofuran and propionitrile), chlorinated solvents (e.g. dichloromethane, dichloroethane, chloroform) and water.

5. The process according to any one of claims 1-4, wherein step (i) can be effected at a temperature of more than 40 ℃, preferably more than 50 ℃ and more preferably more than 60 ℃.

6. The method of any one of claims 1-5, wherein at the alkylating agentbWherein each L is independently selected from the group consisting of halides (e.g., Cl, Br, I), sulfonates (e.g.-OSO₂A, wherein A is selected from tolyl, methyl, -CF₃、-CH₂Cl, phenyl and p-nitrophenyl), substituted aryloxy (e.g., -O-Ar, wherein Ar is selected from nitro substituted aryl such as p-nitrophenyl), and hydroxy, more preferably from halides and sulfonates, and most preferably from Cl and Br.

7. The process according to any one of claims 1-6, wherein step (ii) is effected in the presence of a hydrogen source and a hydrogenation catalyst.

8. The process according to claim 7, wherein the hydrogenation catalyst is selected from palladium, platinum, nickel (e.g. Raney nickel) and rhodium catalysts, preferably palladium and platinum catalysts, such as selected from Pd/C, Pt (OH)₂And PtO₂。

9. The method according to claim 7 or claim 8, wherein the hydrogen source is hydrogen gas, for example at a pressure of 1-80 bar, preferably 5-70 bar and more preferably 10-60 bar.

10. The method according to any one of claims 7-9, wherein step (ii) is effected at a temperature of at least 20 ℃, such as at a temperature of 20-70 ℃ and preferably 25-60 ℃.

11. The process according to any one of claims 7-9, wherein step (ii) is effected in the presence of an acid, preferably an acid selected from inorganic acids such as hydrochloric acid and organic acids such as p-toluenesulfonic acid and acetic acid.

12. The method of any one of claims 1-6, wherein the alkylating agentbAnd intermediatescSelected from:

with the proviso that in the presence of an alkylating agentbWherein two L groups together form a group-O-C (O) -O-or at least one L group is selected from-OH, and

wherein step (ii) comprises substeps (iia) and (iib), wherein the conditions of one of the substeps (iia) and (iib) are as described in any one of claims 7 to 11, and the other substeps (iia) and (iib) comprise the replacement of the hydroxyl group with a halogen, preferably Br or Cl and more preferably Br, in a halogenation reaction.

13. The method of any one of claims 1-6, wherein alkylating agentbAnd intermediatescSelected from:

and wherein step (ii) comprises the sub-steps of:

。

14. the process according to claim 13, wherein the conditions of the substeps (iia') are as described in any one of claims 7 to 11.

15. The method of any one of claims 1-12, wherein the alkylating agentbAnd intermediatescSelected from:

。

16. the process according to any one of claims 1-15, wherein the process is a batch process, wherein the fuel additive is produced in a batch quantity of more than 100kg, preferably more than 150kg and more preferably more than 200 kg.

17. The process of any one of claims 1-15, wherein the process is a continuous process.

18. The process according to any one of claims 1-17, wherein steps (i) and (ii) are effected in a reactor having a volume of at least 500L, preferably at least 750L and more preferably at least 1000L.

19. A fuel additive having the formulae：

Wherein: r₁Is hydrogen;

R₆、R₇、R₈and R₉Each independently selected from hydrogen, alkyl, alkoxy-alkyl, secondary amine and tertiary amine groupsClustering;

n is a number of 0 or 1,

wherein the fuel additive is obtainable by the process according to any one of claims 1-18.

20. A method for preparing a fuel for a spark-ignition internal combustion engine, the method comprising:

preparing a fuel additive using the method of any one of claims 1-18; and

blending the fuel additive with a base fuel.

21. A fuel for a spark-ignition internal combustion engine, the fuel comprising the fuel additive of claim 19 and a base fuel.